Structural highlights
Publication Abstract from PubMed
CTX-M is the most prevalent family of extended-spectrum beta-lactamases. We recently developed a tetrazole-derived non-covalent inhibitor of CTX-M-9. Here, we present biochemical and microbiological activity of this inhibitor across a representative panel of serine beta-lactamases and Gram-negative bacteria. The compound displayed significant activity against all major subgroups of CTX-M, including CTX-M-15, while exhibiting some low-level inhibition of other serine beta-lactamases. Complex crystal structures with CTX-M-14 S237A mutant and CTX-M-27 illustrate the binding contribution of specific active site residues on the beta3 strand. In vitro pharmacokinetic studies revealed drug-like properties and positive prospects for further optimization. These studies suggest that tetrazole-based compounds can provide novel chemotypes for future serine beta-lactamase inhibitor discovery.
Antibacterial spectrum of a tetrazole-based reversible inhibitor of serine beta-lactamases.,Pemberton OA, Zhang X, Nichols DA, DeFrees K, Jaishankar P, Bonnet R, Adams J, Shaw LN, Renslo AR, Chen Y Antimicrob Agents Chemother. 2018 May 29. pii: AAC.02563-17. doi:, 10.1128/AAC.02563-17. PMID:29844038[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pemberton OA, Zhang X, Nichols DA, DeFrees K, Jaishankar P, Bonnet R, Adams J, Shaw LN, Renslo AR, Chen Y. Antibacterial spectrum of a tetrazole-based reversible inhibitor of serine beta-lactamases. Antimicrob Agents Chemother. 2018 May 29. pii: AAC.02563-17. doi:, 10.1128/AAC.02563-17. PMID:29844038 doi:http://dx.doi.org/10.1128/AAC.02563-17
